Exposure to tobacco and alcohol are the major risk factors involved in oral cancer susceptibility. Genetic susceptibility plays a role, with variation in the genes involved in metabolism of alcohol, particularly the ADH gene cluster on human chromosome 4, appearing to contribute to disease. The International Agency for Research on Cancer (IARC) has developed a multicentre case-control study (The IARC multicenter oral cancer study) of approximately 1600 cases and 1600 control individuals from 9 different countries and three major ethnicities to investigate oral risk factors, notably exposure to human papillomavirus (HPV), tobacco and alcohol. The goal of the project described in this application is to investigate new findings from a separate large genome wide association study of upper aerodigestive tract cancer in the specific context context of oral cancers. In particular we will investigate 30 genetic variants in the IARC international oral cancer study and investigate how these affect risk in European, Asian and African populations. Public Health Relevance: While exposure to tobacco and alcohol the key risk factors, genetic variation is also thought to play a role in susceptibility to cancers of the oral cavity and pharynx. The goal of this project is to investigate new findings from a separate genome wide association study of upper-areodigestive tract cancer in the specific context of cancers of the oral cavity and pharynx.